Submissions for variant NM_025137.4(SPG11):c.6477+4A>G

dbSNP: rs312262780

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847637	SCV002105753	uncertain significance	Hereditary spastic paraplegia	2018-05-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000034246	SCV002186883	uncertain significance	Hereditary spastic paraplegia 11	2021-07-16	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 41345). This variant has been observed in individual(s) with autosomal recessive hereditary spastic paraplegia (PMID: 18079167). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 34 of the SPG11 gene. It does not directly change the encoded amino acid sequence of the SPG11 protein. It affects a nucleotide within the consensus splice site of the intron.
Genome-Nilou Lab	RCV002467535	SCV002763703	uncertain significance	Amyotrophic lateral sclerosis type 5		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467536	SCV002763704	uncertain significance	Charcot-Marie-Tooth disease axonal type 2X		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000034246	SCV002763705	uncertain significance	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing
Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL)	RCV000034246	SCV003920825	pathogenic	Hereditary spastic paraplegia 11	2023-04-27	criteria provided, single submitter	research
GeneReviews	RCV000034246	SCV000058186	not provided	Hereditary spastic paraplegia 11		no assertion provided	literature only